Safe and effective beta-lactamase dosing for microbiome protection
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Publication Number
US-11872268-B2
Publication Date
2024-01-16
Expiration Date
Abstract
The present invention relates to, inter alia, safe and effective doses of a beta-lactamase for, e.g. microbiome protection.
Core Innovation
The invention provides a method of protecting a human patient’s gastrointestinal microbiome by administering an effective amount of a pharmaceutical composition comprising a beta-lactamase to a patient undergoing treatment or having recently undergone treatment with a beta-lactam antibiotic. The beta-lactam antibiotic is a penicillin or a cephalosporin, and the beta-lactamase comprises an amino acid sequence having at least 98% identity with SEQ ID NO: 1.
The method further includes the patient undergoing treatment with a proton pump inhibitor, where the proton pump inhibitor is esomeprazole, omeprazole, lansoprazole, rabeprazole, pantoprazole, or dexlansoprazole. The described approach aims to protect the gastrointestinal microbiome during and/or after beta-lactam therapy without substantially reducing systemic antibiotic/plasma levels, with minimal systemic bioavailability and absent from plasma.
The disclosed compositions and regimens include oral, delayed-release enteric formulations intended to support GI microbiome protection during and after beta-lactam antibiotic exposure. The disclosure also supports the role of GI pH modulation to promote earlier enzyme release and earlier degradation of residual beta-lactam antibiotics in chyme.
Claims Coverage
The partial content provides one independent claim defining the core microbiome-protection method and multiple dependent claims that narrow administration timing, specify oral administration of the beta-lactamase, and define microbiome-protection outcomes and maintenance goals.
Proton-pump-inhibitor-associated beta-lactamase microbiome protection
Administering an effective amount of a pharmaceutical composition comprising a beta-lactamase to a human patient undergoing treatment or recently undergoing treatment with a penicillin or cephalosporin beta-lactam antibiotic, wherein the patient is undergoing treatment with a proton pump inhibitor selected from esomeprazole, omeprazole, lansoprazole, rabeprazole, pantoprazole, or dexlansoprazole, and wherein the beta-lactamase comprises an amino acid sequence having at least 98% identity with SEQ ID NO: 1 to protect the gastrointestinal microbiome.
Simultaneous antibiotic and beta-lactamase administration
Practicing the method by administering the beta-lactam antibiotic and beta-lactamase simultaneously.
Oral beta-lactamase administration
Further specifying that the beta-lactamase is administered orally.
Protection against selected microbiome-mediated disorders
Providing microbiome protection by treating or preventing a microbiome-mediated disorder selected from antibiotic-induced adverse effects, C. difficile infection, and a C. difficile-associated disease.
Maintenance of a normal intestinal microbiota
Maintaining a normal intestinal microbiota by achieving a healthy microbiota balance and a healthy ratio or distribution.
Protection of the gastrointestinal microbiome is achieved by administering an oral beta-lactamase with at least 98% identity to SEQ ID NO: 1 to patients receiving penicillin or cephalosporin beta-lactam antibiotics while they are also treated with a specified proton pump inhibitor, with further narrowing to simultaneous administration and defined microbiome-protection outcomes such as C. difficile-related disorders and maintaining a healthy intestinal microbiota balance or distribution.
Stated Advantages
Protects the gastrointestinal microbiome during and/or after beta-lactam antibiotic therapy.
Inactivates residual antibiotics in intestinal chyme without substantially reducing systemic antibiotic/plasma levels.
Supports minimal systemic bioavailability and absent from plasma.
Provides microbiome protection by treating or preventing antibiotic-induced adverse effects and C. difficile infection/C. difficile-associated disease.
Maintains a normal intestinal microbiota with a healthy balance and healthy ratio or distribution.
Documented Applications
Protecting a human patient’s gastrointestinal microbiome during or after treatment with beta-lactam antibiotics, including patients undergoing treatment with a proton pump inhibitor.
Treating or preventing microbiome-mediated disorders including antibiotic-induced adverse effects, C. difficile infection, and C. difficile-associated disease.
Applying the method to antibiotic-induced adverse effects and/or CDI or C. difficile-associated disease.
Maintaining a normal intestinal microbiota by achieving a healthy microbiota balance and healthy ratio or distribution.
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